1. Field of the Invention
The present invention relates to t Kawasaki Disease, including typical Kawasaki Disease and a typical Kawasaki Disease. More particular, the invention relates to methods and systems for the diagnosis of Kawasaki Disease.
2. Description of the Prior Art
Kawasaki Disease (xe2x80x9cKDxe2x80x9d hereafter) is first described by Tomisaku Kawasaki in 1967 in Japan. KD is an acute systemic vasculitis particularly occurring in childhood under the age of 5. The disease is characterized by prolonged fever, reddening and indurative edema of hands and feet and multiple clinical and biochemical features of inflammation and most common complications of coronary artery abnormality (xe2x80x9cCAAxe2x80x9d hereafter). KD has been recognized worldwide in children of all racial backgrounds. Over 125,000 cases have been reported through the end of 1994 (Shulman et al., Kawasaki Disease, Pediatric Rheumatology, 42:1205-1222, 1995); the annual incidence in Japan is 67 per 100,000 children under the age of 5; in Taiwan, this number is estimated to be 32 per 100,000 children under the age of 5. In the United States, emerging cases range from 3,000 to 5,000 annually. The disease is most commonly manifests as acute coronary artery lesions. If left untreated, serious complications and death may result.
Currently, a specific test for the diagnosis of KD does not exist. It is very difficult to diagnose KD definitely in an early stage because its etiology remains unclear. Based on the epidemiologic and clinical features of KD, it is suggested that KD may be caused by an infectious agent which has not been identified, but confirmed that KD would lead to immune-mediated syndromes in certain genetically predisposed individuals.
KD is diagnosed clinically by identifying 5 out of 6 symptoms, including a fever lasting more than 5 days, conjunctiva injection, changes in the lips and oral mucosa, changes in the peripheral extremities, skin rash, and cervical lymphadenopathy (Morens DM. et al., National Surveillance of Kawasaki Disease. Pediatrics 65:21-25, 1980). Normally, the 5 out of the 6 symptoms are regarded as the criteria for determining KD.
Because of the varying severity and inconstant appearance of clinical manifestations, some patients with KD in whom characteristic coronary artery abnormalities developed after the onset of the illness that did not meet the criteria for determining KD, are diagnosed with what is called Atypical Kawasaki Disease (Rowley et al., Incomplete Kawasaki Disease with Coronary Artery Involvement. Eur J. Pediatr, 151:577-580, 1992). The diagnosis of AKD is difficult since those patients only have three or four out of six symptoms. Actually, to meet all of the criteria for determining KD is too strict to find AKD, which often results in sequels of myocardial infarction of sudden death. ALL patients with coronary artery vasculitis have less than four of the symptoms (Boven et al., Atypical Kawasaki Disease Citation: An Often Missed Diagnosis; (Joffe et al., Atypical and Complicated Kawasaki Disease in Infants, Do We Need Criteria?, West J. Med, 162:322-327, 1995). Coronary Artery Abnormality (CAA hereafter) is the most distinctive and fearsome complication accompanying KD, since it may cause sudden death from cardiac disease during the convalescent stage (Syed et al., Coronary Artery Aneurysm: A Review, Progress in Cardiovascular Diseases, 40:77-84, 1977). Early therapy with intravenous immunoglobulin (IVIG), sometimes combined with aspirin, was found to be effective in reducing the incidence of CAA in the acute phase (Furusho et al., Japanese Gamma Globulin Trials for Kawasaki Disease. In Shulman ST, ed. Kawasaki Disease. New York: AIan R. Liss Inc. pp. 425-432, 1986; Newburger et al., The Treatment of Kawasaki Syndrome With Intravenous Gamma Globulin. N Eng J Med 315:341-347, 1986).
A method of confirming the diagnosis of KD in patients by using anti-tumor necrosis factor monoclonal antibody was disclosed in U.S. Pat. No. 5,075,236. Further, U.S. Pat. No. 5,286,623 provided a method for screening for the possibility of KD in a patient which comprises assaying a T cell receptor containing a sample taken from said patient to determine the level of Vb2 or Vb8.1 by immunoassay or by measuring Vb2 or Vb8.1 mRNA. A method for screening for the possibility of KD in patients by using an antibody which specifically binds to toxic shock syndrome toxin-1 (TSST-1) was disclosed in U.S. Pat. No. 5,470,716. However, none of the above-mentioned references provides a precise diagnosis or detection of KD since the substances to be detected in those known methods would also be present in patients suffering from other diseases.
Given the above, there is an urgent and extremely important need to find an effective and specific method for diagnosis of KD and AKD at early stages so that a strategy for the treatment of KD or AKD can be decided earlier.
One objective of the invention is to provide a method for diagnosing Kawasaki disease (KD) in a patient suspicious of KD by using as an index a ratio of the blood level of haptoglobin (Hp) to the blood level of apolipoprotein AI (AI) in said patient.
In particular, the claimed invention provides a method for diagnosing Kawasaki disease (KD) in a patient suspicious of KD comprising:
(a) measuring the blood level (w/v) of haptoglobin (Hp) in said patient to obtain a value A;
(b) measuring the blood level (w/v) of apolipoprotein AI (Apo AI) in said patient to obtain a value B;
(c) calculating the ratio of A/B as an index;
(d) comparing the index A/B obtained in step (c) with an cut off value wherein based on the cut off value, the predictive value of a positive test (PPV) is higher than 70%; and
(e) diagnosing said patient as suffering from KD if the index is higher than the cut off value.
Another objective of the invention is to provide a method for diagnosing atypical or typical Kawasaki disease in a patient suspicious of KD to determine the strategy of the treatment of KD earlier by using the phenotype of haptoglobin.
The invention also provides a system for diagnosing KD and/or AKD in a patient suspicious of KD.